Dental caries is a widespread disease and, despite public health and research efforts, the disease remains difficult to prevent. In the United States, the generous use of sucrose by each socioeconomic level as a dietary constituent may magnify the occurrence of caries. A valuable and effective means of reducing the incidence of dental caries has been the use of fluoride in water supplies and dentifrices. Other means of inhibiting the formation of caries in mass populations have been suggested, but remain unproven. These include the use of selected antibiotics, the possible stimulation of an individual's local immune system, and the use of certain enzymes, such as dextranases. In the proposed research, we plan to synthesize and test several sucrose derivatives as potential anti-caries agents. We have established that the site-directed irreversible enzyme inhibition of the glucosyltransferases of streptococcus mutans is an effective means of preventing the formation of glucans from sucrose. The glucosyltransferases are thought to be critical enzymes in the development of carious lesions. The research plan is to design, synthesize and characterize the sucrose analogue. The derivative will then be tested for its inhibition of glucosyltransferase preparations, its inhibition of the adherence of streptococcus mutans to saliva-coated hydroxyapatite beads, its possible mutagenic potential, and finally, its ability to prevent carious lesions in an animal system. This reseach may reveal new and important leads to preventing dental caries, and concomitantly enhance the willingness of the public to use sucrose with confidence. Ideally, properly designed and tested sucrose derivatives could be added to foods, beverages and improve the oral health of the public.